Inhibitory effect of interleukin-4 on the in vitro growth of Ph1-positive acute lymphoblastic leukemia cells.
Inhibitory effect of interleukin-4 on the in vitro growth of Ph1-positive acute lymphoblastic leukemia cells.
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IL-4对Ph1阳性急性淋巴细胞白血病细胞体外生长的抑制作用。
DOI：
10.1182/blood.v78.6.1574.bloodjournal7861574
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发表时间：
1991
期刊：
影响因子：
20.3
通讯作者：
T. Miyazaki
中科院分区：
文献类型：
--
作者：
M. Okabe;Y. Kuni;T. Sugiwura;M. Tanaka;T. Miyagishima;I. Saiki;T. Minagawa;M. Kurosawa;T. Itaya;T. Miyazaki
本文研究了重组人白细胞介素4（rhIL-4）对人白血病细胞体外生长的影响，发现rhIL-4对Ph_1阳性急性淋巴细胞白血病（Ph_1 ALL）和三种Ph_1 ALL细胞株的生长均有抑制作用。然而，没有抑制作用，被认为是在Ph 1阳性白血病细胞系来自慢性髓性白血病患者的原始细胞危机和各种类型的Ph 1阴性白血病细胞，包括B系白血病细胞。在IL-4受体（IL-4 R）的流式细胞术测定中，所有三种Ph 1阳性ALL细胞系均显示其细胞表面存在IL-4 R，并且通过加入针对rhIL-4的单克隆或多克隆抗体，IL-4对Ph 1阳性ALL细胞生长的依赖性抑制被废除。其他细胞因子，包括IL-2、IL-3、粒细胞-巨噬细胞集落刺激因子（CSF）、粒细胞-CSF和IL-6，对Ph 1-ALL细胞的生长无抑制作用，但肿瘤坏死因子-α（TNF-α）和干扰素（IFN）-α、-β和-γ在高浓度下显示轻微抑制作用。在Ph 1阳性ALL细胞中，rhIL-4诱导的生长抑制作用并没有被IFN-γ或TNF-α抗体的加入所消除。此外，这些细胞在暴露于rhIL-4后未显示出IFN-α、IFN-β或IFN-γ或TNF-α的显著产生，因此表明rhIL-4对Ph 1阳性ALL细胞的生长抑制与IL-4刺激这些因子的产生无关。rhIL-4对这些Ph 1阳性ALL细胞中的酪氨酸激酶活性产生显著抑制作用，类似于抑制这些细胞中酪氨酸激酶活性的酪氨酸激酶抑制剂Herbimycin A。我们的研究结果表明，rhIL-4的临床评价可能为Ph 1阳性ALL患者提供有希望的治疗可能性。
We investigated the effect of recombinant human interleukin-4 (rhIL-4) on the in vitro growth of human leukemia cells in liquid culture and 3H-thymidine incorporation and found inhibitory effects on the growth of leukemic cells from patients with Ph1-positive acute lymphoblastic leukemia (Ph1 ALL) and three Ph1 ALL cell lines. However, no inhibitory effects were seen in Ph1-positive leukemic cell lines derived from patients with chronic myelogenous leukemia in blast crisis and various types of Ph1-negative leukemia cells, including B-lineage leukemia cells. In a flow cytometry assay of IL-4 receptor (IL-4R), all three Ph1-positive ALL cell lines showed the presence of IL-4R on their cell surfaces, and the IL-4-dependent inhibition on the growth of Ph1-positive ALL cells was abrogated by the addition of either monoclonal or polyclonal antibodies against rhIL-4. Other cytokines, including IL-2, IL-3, granulocyte-macrophage colony-stimulating factor (CSF), granulocyte-CSF, and IL-6, showed no inhibitory effects on the growth of Ph1-ALL cells, but tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN)-alpha, -beta, and -gamma displayed slight inhibitory effects in a high concentration. The growth inhibition induced by rhIL-4 in the Ph1-positive ALL cells was not abrogated by the addition of antibodies against either IFN-gamma or TNF-alpha. Furthermore, these cells showed no significant production of IFN-alpha, -beta, or -gamma or TNF-alpha after exposure to rhIL-4, thus indicating that the growth inhibition of Ph1-positive ALL cells by rhIL-4 is not associated with IL-4-stimulating production of these factors. rhIL-4 caused significant inhibition of the tyrosine kinase activity in these Ph1-positive ALL cells, similar to Herbimycin A, an inhibitor of tyrosine kinase that inhibited the tyrosine kinase activity in these cells. Our finding suggests that the clinical evaluation of rhIL-4 may offer promising therapeutic possibilities for patients with Ph1-positive ALL.
IL-2 信号传导机制：通过单一受体和转导途径介导不同结果。
DOI：
10.1126/science.2492678
发表时间：
1989
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Tigges,MA;Casey,LS;Koshland,ME
通讯作者：
Koshland,ME